The present set of embodiments relate to a bioproduction system, method, and apparatus for creating a scalable bioreactor system. Specifically, the present set of embodiments enable the determination of bioreaction performance characteristics of a commercial scale by matching operational parameters between a small test scale bioreaction to that of a commercial scale bioreaction. The system and methods do not rely on simply making bioreactor apparatuses across scales the same dimensionally which would not account for differences in fluid dynamic properties between very small to very large volumes, but requires tuning of a variety of systems (mixing assembly, sparger system, and headspace airflow system) in conjunction with one another to achieve predictive outcomes.

A cell culture apparatus is provided, including a storage tank including one or a plurality of cell culture units, in which the cell culture unit includes a culture chamber having an inner surface-side space in which a culture solution is stored, a permeable membrane having a first surface to which cells are adherable and a second surface opposite to the first surface, the first surface facing the inner surface-side space, a culture solution storage chamber that stores the culture solution, a culture solution introduction flow path that introduces the culture solution in the culture solution storage chamber to the inner surface-side space, and a culture solution discharge flow path that sends, to the culture solution storage chamber, the culture solution which permeates through the membrane from the inner surface-side space and flows into an outer surface-side space that the second surface of the membrane faces.

Gas permeable devices and methods are disclosed for cell culture, including cell culture devices and methods that contain medium at heights, and certain gas permeable surface area to medium volume ratios. These devices and methods allow improvements in cell culture efficiency and scale up efficiency.

Described herein are methods and related compositions for inducing differentiation of human pluripotent stem cells (hPSCs) into hemogenic endothelium with pan-myeloid potential or restricted potential, by forced expression in the hPSCs of a combination of transcription factors as described herein.

A method for producing pancreatic endocrine cells, including introducing (A), (B), (C), or (D) into somatic cells: (A) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof; (B) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and Pdx1 gene or gene product(s) thereof (C) GLIS1 gene or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, Pdx1 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof and (D) mutated GLIS1 gene having 85%-sequence-identity to base sequence of SEQ ID NO: 1 or 2 or gene product(s) thereof, Neurogenin3 gene or gene product(s) thereof, and MafA gene or gene product(s) thereof.

An object of the present invention is to provide a novel method which enables convenient preparation of cells exhibiting functions close to that of intestinal epithelial cells of living bodies, and use of the method. The differentiation of induced pluripotent stem cells into intestinal epithelial cells is induced by step of differentiating induced pluripotent stem cells into endoderm-like cells; step of differentiating the endoderm-like cells obtained in step into intestinal stem cell-like cells; and step of differentiating the intestinal stem cell-like cells obtained in step into intestinal epithelial cell-like cells, wherein step includes culture in the presence of a MEK1 inhibitor, a DNA methyltransferase inhibitor, a TGF-β receptor inhibitor, and EGF and under the condition that cAMP is supplied to the cells.

Described herein are specific CHO genomic sites for targeted insertion of exogenous genes. The sites are located within a sequence selected from SEQ ID NOs: 1-16.

The present disclosure features methods and compositions for modulating lipid metabolism to achieve improved production and quality of recombinant products, such as next generation biologics. Modulation of lipid metabolism as described herein includes, for example, introducing a lipid metabolism modulator described herein to a cell or a cell-free system. Also encompassed by the present disclosure are engineered cells with improved production capacity and improved product quality, methods for engineering such cells, and preparations and mixtures comprising the products from such cells.

The instant disclosure is directed to a method for vascularizing a pancreatic islet comprising culturing the pancreatic islet or β-cells with an endothelial cell comprising an exogenous nucleic acid encoding an ETV2 transcription factor under conditions wherein the endothelial cell expresses the ETV2 transcription factor. The instant disclosure is further directed to a method for making a vascularized β-cell organoid comprising culturing the pancreatic islet or β-cells with an endothelial cell comprising an exogenous nucleic acid encoding an ETV2 transcription factor under conditions wherein the endothelial cell expresses the ETV2 transcription factor. Disclosed also are vascularized islets and vascularized β-cell organoids produced by the methods of the instant disclosure, as well as methods for using the same.

A method of producing a three-dimensional cell structure includes producing a mixture of a cell cluster including an endothelial cell, an extracellular matrix component, and a polymer electrolyte, removing a liquid from the mixture to obtain a cell aggregate, and culturing the cell aggregate in a medium to obtain a three-dimensional cell structure with a thickness greater than 150 μm and having a vascular network. The extracellular matrix component is collagen or a collagen analog, and the polymer electrolyte is heparin or a heparin analog having a final concentration of 0.001 mg/mL or higher in the mixture.